Prospective validation of the 4C prognostic models for adults hospitalised with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol.

Purpose: To prospectively validate two risk scores to predict mortality (4C Mortality) and in hospital deterioration (4C Deterioration) among adults hospitalised with coronavirus disease 2019 (covid-19). Methods: Prospective observational cohort study of adults (age ≥18 years) admitted or first assessed for covid-19 in hospital and recruited into the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study in 306 hospitals across England, Scotland, and Wales. Patients were recruited between 27th August 2020 and 17th February 2021, with at least four weeks follow-up before final data extraction. The main outcome measures were discrimination and calibration of models for in-hospital deterioration (defined as any requirement of ventilatory support or critical care, or death) and mortality, incorporating predefined subgroups. Results: 76 588 participants were included, of whom 27 352 (37.4%) deteriorated and 18 211 (25.1%) died. Both the 4C Mortality (0.78 [0.77 to 0.78]) and 4C Deterioration scores (pooled Cstatistic 0.76 [95% CI 0.75 to 0.77]) demonstrated consistent discrimination across all nine NHS regions, with similar performance metrics to the original validation cohorts. Calibration remained good and was demonstrated to be stable (4C Mortality: slope 1.09, calibration-in-the-large 0.12; 4C Deterioration: 1.00, -0.04), with no need for temporal recalibration during the second wave of hospital admissions. Conclusion: Both 4C risk stratification models demonstrate consistent performance to predict clinical deterioration and mortality in a large prospective 2nd wave validation cohort of UK patients. Despite recent advances in the treatment and management of adults hospitalised with covid-19, both scores can continue to inform clinical decision making.